A number of medical devices that function as implants in the body require a supply or flux of specific biochemicals from the tissue surrounding them for their function. One example of such a device is a type of implanted biochemical-specific sensor known as the “enzyme electrode,” which is used to monitor the bodily concentration of key metabolites such as glucose, lactate, and pyruvate. Information about the concentration of such metabolites can be of benefit in devising therapies for diseases in which these metabolites may play important roles. Certain sensors for these metabolites function on the basis of a chemical reaction between the dissolved, polar molecule of interest and the apolar molecule oxygen, which polar and apolar molecules are supplied as fluxes from the bodily tissues surrounding the implant into a reaction zone within the implant. A chemical product of this reaction or unconsumed oxygen itself can be detected electrochemically to provide an indication of the concentration of the metabolite of interest.
A limitation to the use of such implanted biosensors is that the concentrations of the metabolites of interest are typically substantially higher than the concentration of the oxygen coreactant. For example, the typical concentration of glucose in the blood is about 4 to about 20 mM, whereas a typical concentration of oxygen in blood plasma may be only about 0.05 to about 0.1 mM. Oxygen concentrations in other tissue fluids may be even lower. As the chemical reaction, and thus, the sensor signal, is limited by the reactant that is present in the sensor's reaction zone at lowest concentration, an implanted sensor of simple construction would remain limited by oxygen and would therefore be insensitive to the metabolite of interest. There is, therefore, a need for differential control of the permeability of the sensor membrane to restrict or modulate the flux of the metabolite of interest and provide a stoichiometric equivalent or excess of oxygen in the reaction zone. The sensor incorporating a membrane can then be sensitive to the metabolite of interest over the physiologic range. Also, for successful function of the implanted medical device, the membrane material exposed to the bodily tissue must further be biocompatible, or elicit a favorable response from the body.
Another example of the application of biocompatible membranes with controlled differential permeability is in encapsulation of living tissues, cells, cell derivations, or other biochemically-active constructs used in implant devices to restore biological function that has been lost or compromised due to disease or accident. An example is the isolation and encapsulation of functional Islets of Langerhans from the pancreas of healthy human or cross-species donors or cadavers, or similar cells derived from cultures for implantation in individuals with diabetes. An important purpose of the membrane in this application is to allow diffusional access of oxygen, glucose and nutrients from tissues of the recipient. In order to achieve optimal function of the implanted tissue and avoid toxicity due to substrate imbalances, differential control of membrane permeability is of great importance. By limiting the ingress of potentially damaging cells or molecules or by limiting the egress of cytokines or other molecules that could trigger a response from the host, the membrane can also provide protection against immunological or other biochemically-mediated attack.
Other applications where differential control of permeability is advantageous include: bioreactors containing enzymes, cells, or living tissues; membranes of artificial kidney devices that function by differential removal of metabolic waste products from blood or biological fluids; membranes of artificial respiratory devices that function by controlling the gas content of blood or biological fluids; and various implanted drug delivery devices. In these cases, differential control of membrane permeability can substantially enhance the function of the device.